Unlocking the Potential of Arginine Deprivation Therapy - Recent Breakthroughs and Promising Future for Cancer Treatment

Sep 24, 2026

Uploaded by Kyle

Arginine is a semi-essential amino acid supporting protein synthesis and essential cellular functions. Recent findings indicate it also contributes to wound healing, cell division, ammonia metabolism, immune regulation, and hormone biosynthesis, processes closely tied to tumor growth. Because cancer cells may become arginine auxotrophs after metabolic reprogramming, renewed interest has emerged in arginine deprivation as an anticancer strategy. Multiple therapies have entered clinical trials, using engineered arginine-degrading enzymes to achieve safe, effective tumor cell death alone or with other treatments.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages36

Reading Time1 h 31 min

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Abstract

Introduction

Arginine and cancer cell dependence

Systemic amino acid deprivation concept

Arginine sources and semi-essential status

Metabolic roles of arginine

Review Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment Yu-De Chu 1, Ming-Wei Lai 1,2,* and Chau-Ting Yeh 1,3, * Citation: Chu, Y.-D.; Lai, M.-W.; Yeh, C.-T. Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment. Int. J. Mol. Sci. 2023, 24, 10668. [https://](https://)[ ](https://)[doi.org/10.3390/ijms241310668](doi.org/10.3390/ijms241310668) Academic Editor: Bernhard Biersack Received: 23 May 2023 Revised: 19 June 2023 Accepted: 20 June 2023 Published: 26 June 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; [yudechu@cgmh.org.tw](yudechu@cgmh.org.tw) 2 Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan 333, Taiwan 3 Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan * Correspondence: [a22141@cgmh.org.tw](a22141@cgmh.org.tw) (M.-W.L.); [chauting@cgmh.org.tw](chauting@cgmh.org.tw) (C.-T.Y.) Abstract: Arginine is a semi-essential amino acid that supports protein synthesis to maintain cellular functions. Recent studies suggest that arginine also promotes wound healing, cell division, ammonia metabolism, immune system regulation, and hormone biosynthesis—all of which are critical for tumor growth. These discoveries, coupled with the understanding of cancer cell metabolic reprogramming, have led to renewed interest in arginine deprivation as a new anticancer therapy. Several arginine deprivation strategies have been developed and entered clinical trials. The main principle behind these therapies is that arginine auxotrophic tumors rely on external arginine sources for growth because they carry reduced key arginine-synthesizing enzymes such as argininosuccinate synthase 1 (ASS1) in the intracellular arginine cycle. To obtain anticancer effects, modiﬁed arginine-degrading enzymes, such as PEGylated recombinant human arginase 1 (rhArg1-PEG) and arginine deiminase (ADI-PEG 20), have been developed and shown to be safe and effective in clinical trials. They have been tried as a monotherapy or in combination with other existing therapies. This review discusses recent advances in arginine deprivation therapy, including the molecular basis of extracellular arginine degradation leading to tumor cell death, and how this approach could be a valuable addition to the current anticancer arsenal. Keywords: arginine deprivation cancer therapy; ADI-PEG 20; rhArg1-PEG; BCT-100; arginine auxotrophic cancer; circulating arginine; biomarker 1. Introduction Amino acids are vital components for protein synthesis in mammalian cells, particularly in rapidly dividing cells such as those in malignant tumors [1,2] . However, their functions extend beyond protein synthesis and encompass various physiological events, including the regulation of signaling transduction, gene expression, antioxidative responses, metabolic reprogramming, and immunity [3] . Notably, cancer cells often exhibit an auxotrophy to speciﬁc amino acids, which has been considered a hallmark in several cancer types [4,5] . This results in their dependency on the uptake of exogenous amino acids to meet the demands for rapid growth and metabolic processes. This phenotype has led to the development of a novel therapeutic concept of systemic amino acid deprivation, which aims to limit the supply of speciﬁc amino acids to cancer cells and consequently impair their growth and proliferation [6,7] . Therefore,

FAQs

Why is arginine deprivation being explored for cancer treatment?

Arginine supports multiple tumor-relevant processes, and cancer cell metabolic reprogramming can create arginine auxotrophy, making tumors dependent on external arginine for growth. Limiting extracellular arginine can therefore impair proliferation and contribute to tumor cell death.

What are the main therapies used to deprive tumors of arginine?

The review highlights engineered arginine-degrading enzymes, including PEGylated recombinant human arginase 1 (rhArg1-PEG) and arginine deiminase (ADI-PEG 20). These have been evaluated in clinical trials as monotherapy or in combination with other treatments.

How do arginine deprivation strategies achieve anticancer effects at the molecular level?

Arginine auxotrophic tumors rely on external arginine because key synthesis enzymes in the intracellular arginine cycle, such as ASS1, are reduced. Degrading extracellular arginine lowers available arginine, leading to tumor cell death.

Sep 24, 2026

Uploaded by Kyle